November 2016 patents
Innovations in cancer vaccines, microfluidic devices, reconfigurable surfaces, soft actuators, quantification of lipoproteins, drug delivery, surfactants, inhibition of necrosis, classroom tools, and much more
Harvard faculty David Mooney, David Weitz, Theodore Betley, Greg Verdine, Joanna Aizenberg, Frank Sacks, John Collier, Junying Yuan, George Church, George Whitesides, Gary King, and Eric Mazur are among the inventors issued U.S. patents during November 2016.
The innovations recognized are as follows:
In situ antigen-generating cancer vaccine
U.S. Patent 9,486,512 (November 8, 2016)
Jaeyun Kim, David J. Mooney, Weiwei Aileen Li, Praveen Arany, and Or Gadish
Abstract: The invention provides compositions and methods for utilizing scaffolds in cancer vaccines.
Scale-up of microfluidic devices
U.S. Patent 9,486,757 (November 8, 2016)
Mark Romanowsky, Adam R. Abate, and David A. Weitz
Abstract: Parallel uses of microfluidic methods and devices for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid are described. In some aspects, the present invention relates generally to flow-focusing-type technology, and also to microfluidics, and more particularly parallel use of microfluidic systems arranged to control a dispersed phase within a dispersant, and the size, and size distribution, of a dispersed phase in a multi-phase fluid system, and systems for delivery of fluid components to multiple such devices.
Synthesis of acyclic and cyclic amines using iron-catalyzed nitrene group transfer
U.S. Patent 9,487,472 (November 8, 2016)
Theodore Alexander Betley and Elisabeth Therese Hennessy
Abstract: The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C—H groups, catalyzed by a FeII-dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more C—H groups, catalyzed by a FeII-dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines.
Stabilized polypeptides as regulators of RAB GTPase function
U.S. Patent 9,487,562 (November 8, 2016)
Raymond E. Moellering and Gregory L. Verdine
Abstract: The present invention provides inventive polypeptides comprising a C terminal RAB binding domain (RabBD) of RAB family interacting proteins (FIPs) stabilized by peptide stapling, and pharmaceutical compositions thereof. Also provided are methods for modulating RAB function comprising contacting an inventive stapled polypeptide with a RAB protein, and methods of treatment associated with modulation of RAB activity. The present invention also provides methods of making the inventive stapled polypeptides by ring closing metathesis of unstapled polypeptide precursors.
Reconfigurable surfaces for information security and protection of physical biometrics
U.S. Patent 9,492,578 (November 15, 2016)
Joanna Aizenberg, Tak Sing Wong, and Michael Bucaro
Abstract: Surfaces for information security and protection of physical biometrics, such as a fingerprint, is described. Such biometric information recording surface includes a plurality of raised structures that can reproduce a biometric information when a body part containing the biometric information is applied to the biometric metric information recording surface. The reproduced biometric information can be completely removed by applying a liquid to the plurality of raised structures without need to apply an external physical contact.
Mechanically programmed soft actuators with conforming sleeves
U.S. Patent 9,492,930 (November 15, 2016)
Abstract: A mechanically programmed actuator includes at least one soft actuator body configured to bend, linearly extend, contract, twist, or combinations thereof when actuated without constraint; an activation mechanism (e.g., a fluid pump) configured to actuate the soft actuator body; and at least one sleeve wrapped around part of the soft actuator body and configured to constrain the soft actuator body inside the sleeve when actuated and to cause the soft actuator body to deform where not covered by the sleeve.
Quantification of lipoproteins
U.S. Patent 9,494,606 (November 15, 2016)
Frank M. Sacks and Jeremy D. Furtado
Abstract: Some aspects of this disclosure provide methods and reagents for the detection of apolipoproteins in a sample, for example, a sample obtained from a human subject. Some aspects of this disclosure provide protocols and reagents for the quantification of lipoproteins and lipoprotein particle populations comprising specific combinations of non-integral apolipoproteins and integral apolipoproteins, which is useful, inter alia, for the detection of diseases such as cardiovascular disease as well as an assessment of the risk of an individual to develop a disease.
Translocation of non-natural chemical entities through anthrax protective antigen pore
U.S. Patent 9,498,538 (November 22, 2016)
Xiaoli Liao, Amy E. Rabideau, Bradley L. Pentelute, Jingjing Ling, Gizem Akcay, and John Collier
Abstract: Disclosed is a new approach for delivering compounds and drugs to the cytosol of living cells through the use of engineered protein transporters. The engineered protein transporters include a pore and a pore specific delivery protein, wherein a reagent such as a drug is attached to one or more of the engineered protein transporters.
Compartmentalized screening by microfluidic control
U.S. Patent 9,498,759 (November 22, 2016)
Andrew Griffiths, David Weitz, Keunho Ahn, Darren R. Link, and Jerome Bibette
Abstract: The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalizing the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.
Fluorocarbon emulsion stabilizing surfactants
U.S. Patent 9,498,761 (November 22, 2016)
Christian Holtze, David A. Weitz, and John Brian Hutchison
Abstract: Surfactants (e.g., fluorosurfactants) for stabilizing aqueous or hydrocarbon droplets in a fluorophilic continuous phase are presented. In some embodiments, fluorosurfactants include a fluorophilic tail soluble in a fluorophilic (e.g., fluorocarbon) continuous phase, and a headgroup soluble in either an aqueous phase or a lipophilic (e.g., hydrocarbon) phase. The combination of a fluorophilic tail and a headgroup may be chosen so as to create a surfactant with a suitable geometry for forming stabilized reverse emulsion droplets having a disperse aqueous or lipophilic phase in a continuous, fluorophilic phase. In some embodiments, the headgroup is preferably non-ionic and can prevent or limit the adsorption of molecules at the interface between the surfactant and the discontinuous phase. This configuration can allow the droplet to serve, for example, as a reaction site for certain chemical and/or biological reactions. In another embodiment, aqueous droplets are stabilized in a fluorocarbon phase at least in part by the electrostatic attraction of two oppositely charged or polar components, one of which is at least partially soluble in the dispersed phase, the other at least partially soluble in the continuous phase. One component may provide colloidal stability of the emulsion, and the other may prevent the adsorption of biomolecules at the interface between a component and the discontinuous phase. Advantageously, surfactants and surfactant combinations of the invention may provide sufficient stabilization against coalescence of droplets, without interfering with processes that can be carried out inside the droplets.
Inhibitors of cellular necrosis and related methods
U.S. Patent 9,499,521 (November 22, 2016)
Junying Yuan, Yijun Zhou, Shan Qian, and Dawei Ma
Abstract: A compound having the following structure (I):
or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.
Transcription activator-like effectors
U.S. Patent 9,499,592 (November 22, 2016)
Feng Zhang, Le Cong, Sriram Kosuri, and George M. Church
Abstract: Provided herein are compositions, kits and methods useful in the construction of designer transcription activator-like effector (dTALE) polypeptides.
Systems and methods for amplification and phage display
U.S. Patent 9,499,813 (November 22, 2016)
Ratmir Derda, Sindy K.Y. Tang, and George M. Whitesides
Abstract: Embodiments of various aspects described herein are directed to amplification of biological entities, for example, for phage display. In one aspect, members of a library of biological entities are encapsulated in separate compartments (e.g., in separate microfluidic droplets) and amplified. For example, by putting members of a phage display library into microfluidic droplets such that no droplet contains more than one member of the library, the library can be amplified without any substantial changes in population distributions, or other artifacts created due to differences in growth rates or amplification between different members of the library. In some cases, the volume of the compartments can be used to control the copy number of a biological entity during amplification. This can be advantageous, for example, in preserving diversity within a library by preventing rapidly amplifying biological entities from outcompeting slowly amplifying biological entities.
Stabilized compounds having secondary structure motifs
U.S. Patent 9,505,801 (November 29, 2016)
Gregory L. Verdine and Christian E. Schafmeister
Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein the peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting the peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized α-helical structure; and (2) contacting the crosslinked stabilized α-helical structure with MDM2.
Flexible robotic actuators
U.S. Patent 9,506,455 (November 29, 2016)
Aaron D. Mazzeo, Stephen A. Morin, Robert F. Shepherd, George M. Whitesides, and William B. Kalb
Abstract: Some embodiments of the disclosed subject matter includes a laminated robotic actuator. The laminated robotic actuator includes a strain-limiting layer comprising a flexible, non-extensible material in the form of a sheet or thin film, a flexible inflatable layer in the form of a thin film or sheet in facing relationship with the strain-limiting layer, wherein the inflatable layer is selectively adhered to the strain-limiting layer, and wherein a portion of an un-adhered region between the strain-limiting layer and the inflatable layer defines a pressurizable channel, and at least one fluid inlet in fluid communication with the pressurizable channel. The first flexible non-extensible material has a stiffness that is greater than the stiffness of the second flexible elastomeric material and the flexible elastomer is non-extensible under actuation conditions.
Cross-classroom and cross-institution item validation
U.S. Patent 9,508,266 (November 29, 2016)
Gary King, Brian Lukoff, and Eric Mazur
Abstract: Anonymous pretesting items for subsequent presentation to participants in a group enable an instructor to validate responses and revise the items accordingly.